Amphiphilic Protoporphyrin IX Derivatives as New Photosensitizing Agents for the Improvement of Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a non-invasive therapeutic modality based on the interaction between a photosensitive molecule called photosensitizer (PS) and visible light irradiation in the presence of oxygen molecule. Protoporphyrin IX (PpIX), an efficient and widely used PS, is hampered in clinical PDT by its poor water-solubility and tendency to self-aggregate. These features are strongly related to the PS hydrophilic–lipophilic balance. In order to improve the chemical properties of PpIX, a series of amphiphilic PpIX derivatives endowed with PEG550 headgroups and hydrogenated or fluorinated tails was synthetized. Hydrophilic–lipophilic balance (HLB) and log p-values were computed for all of the prepared compounds. Their photochemical properties (spectroscopic characterization, photobleaching, and singlet oxygen quantum yield) were also evaluated followed by the in vitro studies of their cellular uptake, subcellular localization, and photocytotoxicity on three tumor cell lines (4T1, scc-U8, and WiDr cell lines). The results confirm the therapeutic potency of these new PpIX derivatives. Indeed, while all of the derivatives were perfectly water soluble, some of them exhibited an improved photodynamic effect compared to the parent PpIX.